This project includes both conceptual analysis of the current federal regulations developed for the protection of children involved in research and empirical studies of the impact of the regulations on pediatric research. Two key developments have precipitated this reassessment. First, the emerging interest to involve children more inclusively in pharmaceutical development. This could include research without the prospect of direct benefit such as phase one studies and pharmacokinetic studies. Second, opportunities to obtain genetic material from children involved both in pharmaceutical research and epidemiological research are increasing. The risk and benefits of such research need to be considered under the structure of the current regulations but also raise questions about the adequacy of that structure to appropriately capture the issues. One focus this year has been a conceptual analysis of ethical issues in newborn screening research. This paper argues for the use of randomized controlled trials because of scientific value and recommends approaches for addressing ethical concerns about informed consent related to randomized screening. A second focus has been on a survey of pediatric IRB chairs about how they interpret the pediatric regulations. One key finding is the variability about how IRBs interpret the risk levels of different procedures.